T细胞受体
生物
主要组织相容性复合体
CD3型
跨膜蛋白
跨膜结构域
受体
生物物理学
细胞生物学
配体(生物化学)
T细胞
抗原
免疫系统
CD8型
生物化学
遗传学
作者
Lukas Sušac,Mai Tuyet Vuong,Christoph Thomas,Sören von Bülow,Caitlin O’Brien‐Ball,Ana Mafalda Santos,Ricardo A. Fernandes,Gerhard Hummer,Robert Tampé,Simon J. Davis
出处
期刊:Cell
[Elsevier]
日期:2022-08-01
卷期号:185 (17): 3201-3213.e19
被引量:67
标识
DOI:10.1016/j.cell.2022.07.010
摘要
The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγε2ζ2 complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements.
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